Worse Cosmesis, Toxicity with Partial- vs. Whole-Breast Irradiation

By: NEIL OSTERWEIL, Skin & Allergy News Digital Network

BOSTON – Cosmetic results were significantly worse after 3 years for women who had accelerated partial-breast irradiation than for women treated with whole-breast irradiation in a randomized clinical trial, investigators found.

Nearly a third (32%) of women who underwent accelerated partial breast irradiation (APBI) with a 3-D conformal technique had cosmetic results rated as fair or poor by a nurse, compared with 19% of women who had undergone whole-breast irradiation (WBI), Dr. Timothy J. Whelan reported at the annual meeting of the American Society for Radiation Oncology.

APBI was also associated with more grade 1 and 2 toxicities than WBI, but there were few grade 3 toxicities with either technique and no grade 4 toxicities, said Dr. Whelan, a radiation oncologist at the Juravinski Cancer Centre in Hamilton, Ont.

"This increase in toxicity may have resulted from limited conformality of the 3-D conformal approach, the short time between the fractions – radiation with APBI was given twice a day with 6 hours between the fractions, which may not have been adequate – and maybe due to the asymmetric nature of partial breast irradiation itself, given that it’s only given to part of the breast," he said at a press briefing.

Trading Convenience for Toxicity?

APBI – in which a large dose per fraction of external beam radiation is given only to the surgical cavity with an additional safety margin – allows radiation therapy to be delivered in 1 week or less, making it an attractive alternative to multifraction therapy that can stretch over many weeks.

But it is still not clear whether APBI trades poorer outcomes for convenience, Dr. Whelan said. He and colleagues in Canada, Australia, and New Zealand conducted the RAPID trial (Randomized Trial of Accelerated Partial-Breast Irradiation Using 3-D Conformal External Beam Radiation Therapy) to find out. The study compared the efficacy and safety of the two modalities in women over 40 years of age with invasive or noninvasive breast cancers smaller than 3 cm.

Investigators enrolled 2,135 patients and randomized them to receive either WBI (1,065 patients) at 50 Gy in 25 fractions or 42.5 Gy in 16 fractions given once daily with or without boost irradiation or 3-D conformal APBI at 38.5 Gy in 10 fractions twice daily (1,070 patients). Cosmetic results were rated by a trained nurse on a global assessment using the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System for Breast Cancer, and for toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Radiologists blinded to treatment type also rated results on digital photographs.

Immediately after radiation, cosmetic results were similar between the groups, with nurse-assessed appearance rated as fair or poor in 17% of women who had WBI, and 19% who had APBI (P = .35). However, an interim toxicity analysis among 850 evaluable patients, showed that at 3 years (2.3 years median follow-up) 13% more of the patients who had undergone APBI had fair or poor cosmesis.

The Jury Is Out

Dr. Whelan noted that the between-group differences were about the same at 5 years, but did not provide data.

"The evidence for partial-breast irradiation is still not very clear. We don’t have very robust evidence about its efficacy, and we just now have recent evidence about its potential toxicities, he said.

Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey in New Brunswick, commented that "the results from the RAPID trial shed further light on the use of accelerated partial-breast irradiation, and emphasize the need to further investigate these fractionation schemes and sort out whether in fact the toxicity from partial-breast irradiation may be slightly worse than with whole-breast irradiation."

Dr. Haffty moderated a briefing where the data were presented, but was not involved in the RAPID trial.

The RAPID trial is supported by the Canadian Institutes of Health Research and Canadian Breast Cancer Research Alliance. Dr. Whelan has received honoraria from AstraZeneca and Novartis. Dr. Haffty reported no relevant disclosures.

Accelerated Partial-Breast Irradiation: The Current State of Our Knowledge

1Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas,
2Department of Radiation Oncology, University of Medicine and
Dentistry of New Jersey: Robert Wood Johnson Medical School &
Cancer Institute of New Jersey, New Brunswick, New Jerseyhttp://www.cancernetwork.com/breast-cancer/content/article/10165/2137303?Quoted Excerpts from the above link:

Guidelines for Treatment

Beginning in
2007, four separate oncologic societies have published guidelines to
assist physicians in selecting patients for APBI offered off protocol (Table 1).
ASTRO organized a task force that published the most detailed set of
guidelines regarding suitability to receive APBI off protocol. This
group recommended that women be classified as “suitable” for APBI
treatment if they are age 60 or older and have invasive ductal carcinoma
(or other favorable histology) ≤ 2 cm; estrogen receptor–positive;
unicentric and unifocal; lymph node–negative; with negative margins (≥ 2
mm); and with no extensive intraductal component (EIC), lymphovascular
space invasion (LVSI), or neoadjuvant therapy.[53] The Groupe Européen
de Curiethérapie and European Society for Therapeutic Radiology and
Oncology (GEC-ESTRO), the American Society of Breast Surgeons, and the
American Brachytherapy Society have all published their own sets of
guidelines.[54-56] These four sets of guidelines were based on older
published studies and the inclusion criteria used therein, coupled with
the judgment of experienced breast radiation oncologists.

APBI: The Future

At least four randomized trials comparing WBI and APBI have been presented thus far, in at least partial form (Table 2);
the results regarding toxicity and efficacy have been mixed. In the
future, we anticipate the publication of results from at least eight
randomized controlled trials comparing WBI and APBI (Table 3).
These trials are being conducted in North America and Europe and in
total will include over 16,000 women. The largest of these, the NSABP
B-39/RTOG 0413 trial, is being conducted in the United States, with
trial closure anticipated shortly.[59] This trial will include 4,300
women with early-stage breast cancer randomly assigned to receive either
WBI (with or without a tumor bed boost) or APBI. In this study, APBI
can be delivered via MIB, single-entry brachytherapy catheter, or
3-dimensional conformal external beam radiation. While the trials now
open vary in terms of patient inclusion criteria and how APBI is
delivered, we expect that they will provide definitive information on
the equivalency of APBI to WBI. However, given the differences in the
mode of APBI delivery in these studies, the findings of one may not be
applicable to the technique used in another, in terms of either tumor
control or toxicity.

Meanwhile, investigators are attempting to
answer such questions as whether MRI can be used to better define
patients who can be treated with APBI, whether brachytherapy-based APBI
can be delivered with fewer total fractions, whether APBI can be
delivered preoperatively, and whether pathologic and surgical margin
findings can be used for patient-specific target definition in
APBI.[60-66]

Conclusion

Given its
greater convenience and perceived better associated quality of life,
APBI is becoming an increasingly popular alternative to conventional WBI
among women with early-stage breast cancer who desire breast
conservation. Published data on APBI are limited largely to findings
from prospectively collected phase II trials, which have shown high
rates of local control in appropriately selected patients. Several sets
of guidelines have been published outlining which patients should be
considered reasonable candidates for treatment with APBI. We anticipate
in the near future the publication of results from a number of
randomized controlled trials including over 16,000 women, which should
better characterize the efficacy and safety of APBI in comparison to
WBI.

Hi Donna - I was wondering which I would do. My RO suggested partial would be good for me, but that was before I told him I am TNBC. So, I am not sure he would change his mind. I have just started AC-T regimen so have a little time before deciding. But, I also felt that with whole breast I would not be cutting any corners, so was leaning towards that. After all this I would be afraid about not treating the whole breast and just partial.

Donna - Is the IMRT a trial type radiation or is something already approved? Many have not heard of it hear in Calif. My doctor does it but says not usually for breast cancer. Plus, they say is not approved by many insurances cause is expensive procedure when the other methods work.

IMRT has been around for a while, but maybe only in the larger cancer centers? I had radiation in 2011 and in my city, there were 3 IMRT machines at the time. Siteman Cancer Center/Washington Univ had 2 of those machines. http://www.siteman.wustl.edu/ContentPage.aspx?id=1098

It was recommended for me since I already had breast reconstruction and it was difficult to get the correct angles of the IM node through the implants. I had no problem with my insurance company covering it.

Rates of local and regional recurrence were identical at 10 years. Distant metastasis occurred less often with WBI (3% versus 6%), whereas contralateral recurrence was more frequent with WBI (9% versus 3%), reported Jessica Wobb, MD, of Beaumont Cancer Institute in Royal Oak, Mich., at the Breast Cancer Symposium.

Disease-free survival, disease-specific survival, and overall survival did not differ significantly between groups, but were consistently higher in WBI-treated patients, Wobb added.

"These data represent one of the only ABPI series with prolonged follow-up and show similar outcomes in a matched group of patients undergoing WBI or APBI," Wobb concluded in a poster presentation.

The findings could represent a case of too little, too late, according to invited discussant David E. Wazer, MD, of Tufts Medical Center in Boston. He reviewed data from the National Cancer Data Base, showing a downturn in the use of brachytherapy after breast-conserving surgery since 2008 and no substantive increase in the use of other forms of APBI going back almost 10 years.

"Why is this happening?" Wazer asked. "I think it is because of toxicity concerns [with APBI], the emergence of alternative short-course hypofractionated whole-breast regimens, and the rise of single-fraction intraoperative radiotherapy."

The emergence of breast-conserving surgery for early-stage breast cancer has been accompanied by the introduction of APBI as an alternative to WBI. As compared with WBI, APBI protocols historically have required less time to complete, offering potentially attractive quality-of-life considerations for patients and providers.

Whether the advantages of APBI came at a cost of cancer outcomes has remained a topic of discussion. Few studies have accumulated long-term data to compare outcomes with APBI and WBI.

Wobb and colleagues presented data from long-term follow-up of 3,009 patients treated with breast conservation at Beaumont from 1980 to 2012. The study population comprised 2,528 women who underwent WBI after surgery and 481 who received catheter- or balloon-based APBI. A matched-pair analysis was performed, including age, cancer stage, and estrogen-receptor (ER) status.

The analysis included 548 of the 3,009 patients. Follow-up averaged 8 years overall but was slightly longer in the WBI group (8.1 versus 7.8 years, P<0.001). Mean tumor size did not differ significantly but was smaller in the APBI group (11.4 versus 13.0 mm). T-stage, ER status, and final surgical margins did not differ significantly between groups. Nodal involvement was more common in the WBI group (14% versus 9%, P=0.07).

Use of adjuvant hormonal therapy was significantly more common in the WBI group (68% versus 54%, P=0.001).

Comparison of 10-year clinical outcomes with APBI versus WBI produced the following results, none of which achieved statistical significance:

Local failure: 4% versus 4%

Contralateral failure: 3% versus 9%

Regional recurrence: 1% versus 1%

Disease-free survival: 91% versus 93%

Cause-specific survival: 93% versus 94%

Overall survival: 75% versus 82%

Excellent cosmesis: 95% versus 94%

In a univariate analysis, significant predictors of ipsilateral breast cancer recurrence with APBI were age (P=0.05) and negative versus close surgical margins (P=0.01). Significant predictors of ipsilateral recurrence with WBI were negative versus close margins (P=0.02) and negative versus positive margins (P<0.001).

Tumor size, stage, nodal status, ER status, hormonal therapy, and chemotherapy did not predict the risk of ipsilateral recurrence with either type of adjuvant radiation therapy.

In reviewing the findings, Wazer questioned whether the two patient groups were truly well matched, noting disparities in tumor size and frequency of hormonal therapy. He also cited a recent report of a small but significantly higher risk of subsequent mastectomy (4% versus 2%) in patients treated with brachytherapy versus WBI.

"There might be a lot of issues with how the [mastectomy] study was done, but nonetheless it has raised sufficient questions for a number of investigators," Wazer said.

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